tbuckley/cabot-search huggingface dataset:
Abstract MP59: Host <i>LCT</i> Genotype Modifies the Relationship Between Milk Intake and Risk of Diabetes Partially Through the Gut Microbiome and Blood Metabolome: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Kai Luo, Guochong Chen, Jiaqian Xing, Jee-Young Moon, Zheng Wang, Bing Yu, Eric Boerwinkle, Gang Hu, Tao Wang, Rob Knight, Robert Burk, Robert Kaplan, Qibin Qi
Journal: Circulation (2023)

Introduction: The relationship between milk intake and risk of diabetes is controversial with substantial ethnical difference. Whether such difference can be partially explained by LCT genotype that varies by ethnical background is unknown. Hypothesis: Higher milk intake is associated with lower risk of diabetes only in lactase non-persistent (LNP) individuals ( LCT rs4988235, GG) but not in LP individuals (AA/AG). Methods: We examined associations of milk intake with incident diabetes (n=7089, 768 incident cases over 6 years), 490 gut microbial species (n=1767) and 624 serum metabolites (n=3110), stratified by LCT genotype in US Hispanics from the HCHS/SOL. We related the identified microbial species and metabolites with metabolic traits and/or incident diabetes. Results: Higher milk intake was associated with lower risk of diabetes in LNP but not in LP individuals (Fig A). Milk intake was associated with different microbial species by LCT genotype, including 13 species specific to LNP individuals (Fig B), especially Bifidobacterium sp. (enriched), which were favorably associated with several metabolic traits (Fig C). In LNP individuals, milk intake was specifically associated with 20 metabolites (Fig D). Metabolites positively associated with milk, especially indolepropinate and β-cryptoxanthin, were favorably associated with metabolic traits and risk of diabetes (Fig E). Opposite patterns were found for metabolites negatively associated with milk, especially for several bile acids and branched chain amino acid metabolites (Fig E). Some of these metabolites are known microbiota related, were correlated with LNP specific milk-related bacteria, and partially mediated the milk-diabetes association in LNP individuals (Fig F). Such associations were not observed for LP specific milk-related bacteria or metabolites. Conclusion LCT genotype may modify the relationship between milk intake and diabetes, with a beneficial association in LNP individuals, partially explained by gut microbiota and serum metabolites.
Abstract P345: Physical Activity and Cardiorespiratory Fitness Among Adolescents With Type 1 and Type 2 Diabetes: A Systemic Review and Meta-Analysis
Authors: Hannah Steiman De Visser, Isaak D Fast, Edward Arevalo, Nicole Askin, Jonathan McGavock
Journal: Circulation (2023)

Background: Physical activity (PA) is a cornerstone in the management of pediatric diabetes, due in part to a dose-response effect on cardiorespiratory fitness (CRF). The extent to which PA and CRF is impaired in children and adolescents with diabetes remains unclear. Hypothesis: We hypothesized that PA and CRF would be lower in children and adolescents with type 1 (T1D) and (T2D) compared to controls. Design and Methods: To test this hypothesis we conducted a systematic review of observational studies in MEDLINE, Embase, the Cochrane Library, and CINAHL from 2000 to April 2022. Cross sectional studies that reported PA and/or CRF for children and adolescents (0-21 years) with T1D, T2D and controls without diabetes were included in the analysis. We excluded studies in adults and those that did not differentiate diabetes type. The main outcomes of interest were objective or subjective measures of PA and direct or indirect measures of CRF. Co-variates extracted from each manuscript included body mass index, sex, measures of socio-economic status, age and ethnicity. A modified risk of bias tool was used to assess the methodological quality of each study. (Prospero registration: CRD42022329303). We used an inverse variance weighted meta-analysis to estimate effect size and precision effects. A random effects model was used. Results: Of 7857 citations retrieved, we included 42 studies with T1D (n=4027 with T1D, n=9699 controls) and 14 studies with T2D (n=581 with T2D, n=1008 controls). 26 and 2 studies included direct and indirect measures of cardiorespiratory fitness respectively. 14 and 26 studies include objective and subjective measures of PA respectively. The standardized mean difference (SMD) was PA [-0.28; 95% CI: -0.46, -0.10; I 2 = 89%] and CRF [-0.30; 95% CI: -0.66, 0.06; I 2 = 92%] were lower children and adolescents with for T1D compared to controls. The SMD for PA [-0.61; 95% CI: -0.98, -0.24; I 2 = 89%] and CRF [-1.20; 95% CI: -1.73, -0.67; I 2 = 91%] were also lower for children and adolescents with T2D compared to controls. The majority of studies were considered a high risk of bias. Conclusions: Children and adolescents with T1D display modestly lower daily PA and CRF compared to controls. Deficits in PA and CRF are more profound among children and adolescents with T2D.
Abstract P146: The Effects of Lifestyle Interventions on Blood Pressure in Postpartum Women: A Systematic Review
Authors: Mara E Murray Horwitz, Grayce S Bredy, Alaina Tabani
Journal: Circulation (2023)

Introduction: One in 3 parous individuals has a pregnancy complication that indicates increased risk for future hypertension, diabetes, or heart disease. Lifestyle modification is recommended to reduce chronic disease risk after complicated pregnancies. However, little is known about the effect of lifestyle interventions on blood pressure in postpartum women. Thus, our objective was to evaluate the effects of postpartum lifestyle interventions on blood pressure. We hypothesized that postpartum lifestyle interventions would be associated with a decrease in blood pressure. Methods: We conducted a systematic literature review of six databases (Google, Google Scholar, Embase, Clinical Trials.gov, Cochrane Central, and PubMed) for relevant articles published through May 12, 2022. We considered for inclusion any randomized controlled trial or quasi-experimental, cohort, or case-control study that evaluated a postpartum lifestyle intervention and included blood pressure as an outcome. We excluded non-English publications and articles published before 2010. Two researchers independently identified eligible publications via title and abstract screening followed by full-text review, then extracted relevant data; a third researcher resolved any discrepancies. Due to the heterogeneity of the included studies, we were not able to conduct statistical testing. Results: In total 2,564 unique publications underwent title and abstract screening, of which 32 underwent full-text review, and eight met the inclusion criteria. Six of the included studies were randomized controlled trials, and five had relatively small sample sizes (&lt;100). In studies that reported race, nearly all participants identified as White (82%-100%). Seven of the studies required participants to have a history of a pregnancy complication, most often preeclampsia. Interventions usually involved diet and exercise counseling; only two included supervised exercise. Mean blood pressure declined from baseline to follow-up in all of the studies, however in none was there a statistically significant difference in blood pressure change between the intervention and control groups. While not statistically significant, the interventions that included supervised exercise appeared to be associated with greater blood pressure reductions when compared with control, than were the unsupervised interventions. Conclusions: In conclusion, we found no statistically significant effects of postpartum lifestyle interventions on blood pressure. Supervised exercise interventions appeared most promising. The evidence is limited to a handful of published studies (n=8) characterized by small sample sizes and a lack of racial diversity. Additional research with more diverse populations and supervised exercise interventions are warranted.
Abstract 34: A Quarter of a Mile More Steps Are Incrementally Associated With Lower Risk of Proximal CVD Events Among Older Adults: Atherosclerosis Risk in Communities (ARIC) Study
Authors: Erin E Dooley, Brady Rippon, Pablo Martinez-Amezcua, Amanda E Paluch, Lisa Pompeii, Priya Palta, Kelley Pettee Gabriel
Journal: Circulation (2023)

Introduction: Steps are an easily interpretable metric that could be used in patient-clinician communication regarding the health benefits of physical activity for cardiovascular disease (CVD). However, most studies are conducted in younger populations with daily steps goals (e.g., 10,000 steps) that may be unsuitable for older adults. Hypothesis: We tested the hypothesis that more daily steps are associated with lower risk of proximal CVD events (within 3.5 years) among older adults (≥70 years). Methods: We analyzed a subsample of participants from the ARIC study visit 6 (2016-17) who wore an accelerometer (ActiGraph GT3X) on the waist ≥3 days for ≥10 hr/day. Daily steps were analyzed continuously and by quartiles. Adjudicated outcomes, through December 2019, included fatal and non-fatal CVD events (coronary heart disease, stroke, and heart failure). Multivariable adjusted Cox proportional hazard models were used to estimate the hazard ratio of CVD events across step measures, adjusted for age, sex, race, education, body mass index (BMI), and accelerometer wear time. Results: Among the 452 adults with step data (mean age = 78.4; 59% women; 20% Black), 7.5% (34/452) had a CVD event over 1,269 person-years of follow-up. Mean (SD) step count was 3447 (1796) steps/day. CVD cumulative incidence was highest among those in the least active step quartile (Q1: &lt;2077 steps/day) (11.5%) compared to the most active quartile (Q4: ≥4453 steps/day) (3.5%). Every 500 steps/day (about 1/4 mile) was associated with a 14% reduced risk of a CVD event (HR = 0.86, 95% CI: 0.76, 0.98). Further, compared to participants in Q1, participants in Q4 had a 77% reduced risk of a proximal CVD event (HR = 0.23, 95% CI: 0.07, 0.83). Cubic spline HR are presented (figure). Conclusions: In this community-based cohort of older adults, every 500 steps (~1/4 of a mile) was associated with a 14% lower risk of a CVD event over 3.5 years of follow-up. Additional follow-up is needed to determine if higher steps prevent or delay CVD or if low steps serve as a biomarker of underlying disease.
Abstract P411: Low Serum Magnesium Predicts Higher Troponin and Lower Ejection Fraction in Acute Coronary Syndrome
Authors: Nikky Bardia, Nupur Shah, Mariam Riad, Mustafeez Ur Rahman, Rajasekhar Mulyala, Alexis Parks, Christopher Malozzi, G. Mustafa Awan, Bassam A Omar
Journal: Circulation (2023)

Background: Low Magnesium levels not only increase the risk of arrhythmias, but are also associated with increased myocardial damage in experimental animal models. The role of Mg levels and Mg supplementation on clinical outcomes after acute coronary syndrome (ACS) in human studies, however, remains controversial. Objective: To determine if low serum Mg levels in patients admitted with an ACS are associated with higher peak troponin I levels and lower left ventricular ejection fraction (EF), both of which are indicators of extensive myocardial damage and are independent markers of poor outcomes. Methods: Data were collected from University Medical Center’s computer system. Clinical lab defines low Mg as a level below 1.8 mg/dL. A total of 369 patients with ACS were identified; 86 had low Mg, and 283 had normal Mg. Data collected included age, gender, revascularization status, serum Mg, peak troponin I, peak CKMB, and EF. Data was analyzed using Student’s t-test. Results: Patients admitted with ACS had significantly higher troponin levels of 32.1 ng/mL when Mg level was &lt; 1.8 mg/dL, compared to 25.9 ng/mL when Mg level was ≥ 1.8 mg/dL (6.2 ng/mL higher; P &lt; 0.05). EF was significantly lower at 45.6% with Mg level of &lt; 1.8 mg/dL, compared to 49.8% with Mg level of ≥ 1.8 mg/dL (4.2% lower; P &lt; 0.05). Peak CKMB, age, gender, and revascularization status were not significantly different between the two groups. Discussion: In our cohort of patient admitted with ACS, we demonstrated a significant correlation between lower Mg levels and troponin level elevation, in addition to lower EF, indicating more extensive myocardial damage, which portends poor cardiovascular outcomes. Even though the role of Mg supplementation in the setting of ACS has been equivocal in the literature, it is likely, based on our findings, that maintaining normal Mg levels in patients at risk of ACS may translate into better outcomes if these patients present with an ACS. Further studies would be needed to examine this hypothesis and shed light on the potential mechanism behind our observations.
Abstract P186: HIV Status, Immune Cell Subsets and Type of Incident Heart Failure
Authors: Samuel Mensah, Suman Kundu, Chung-Chou H Chang, Margaret Doyle, Alex Werekuu, Alexis Kiyanda, Prasad Patil, John Koethe, Hilary A Tindle, Matthew S Freiberg, Kaku So-Armah
Journal: Circulation (2023)

Introduction: Immune dysfunction is a mechanism involved in atherosclerosis; atherosclerotic cardiac events contribute to heart failure (HF) risk. We investigated whether immune cell subtypes were associated with HF and HF types in people with and without HIV. Hypothesis: Six CD4+ and CD8+ T-cell subsets previously associated with atherosclerosis will be associated with increased HF with reduced ejection fraction (HFrEF) risk. Other lymphocyte subsets will be associated with increased HF with preserved ejection fraction (HFpEF) risk. Methods: We measured lymphocyte subsets (T-, B-, and natural killer cells) in the Veterans Aging Cohort Study (VACS) Biomarker Cohort. Primary analyses used Cox proportional hazards models to estimate hazard ratios of HFpEF or HFrEF per standard deviation increment in each of the 6 pro-atherosclerotic T-cell subsets. Secondary analyses used survival random forest analysis to rank the importance of a broader under-studied set of lymphocyte subsets in HF risk prediction and Cox models to estimate HF risk. Results: Among 2174 (66% PWH) participants without prevalent cardiovascular disease, 269 had incident HF (22% HFrEF, 47% HFpEF) over 8.8 years median follow-up time. Participants were predominantly male (&gt;90%) and black (&gt;66%). After adjusting for age, race/ethnicity, cytomegalovirus status, and HIV status, we did not detect associations the 6 T-cell subsets with HFrEF. We detected positive associations of CD4+CD28-, CD4+CD45RA+CD28-CD57+, TH1, TH17 cells with HFpEF. Survival random forest analysis revealed the relative importance of lymphocyte subsets for prediction of HF beyond those previously associated with atherosclerosis (Fig 1). Conclusion: Contrary to hypotheses, pro-atherosclerotic subsets of CD4+ and CD8+ T-cells were associated with HFpEF but not HFrEF. Other lymphocyte subsets previously-understudied for incident human cardiac outcomes were associated with HF incidence. Future work will examine whether these associations differ by HIV status.
Abstract P166: First Trimester Plasma Per- and Polyfluoroalkyl Substance (PFAS) Concentrations and Blood Pressure Trajectories Throughout the Second and Third Trimesters of Pregnancy
Authors: Jordan Arvayo, Briana J Stephenson, Izzuddin Aris, Emma V Preston, Marie-France Hivert, Emily Oken, Sheryl L Rifas-Shiman, Ami Zota, Tamarra James-Todd
Journal: Circulation (2023)

Introduction: Evidence suggests that PFAS exposures increase risk of hypertensive disorders of pregnancy. Prior studies did not examine blood pressure (BP) trajectories during pregnancy – an important outcome to consider since adverse health outcomes can occur without diagnosis of a hypertensive disorder. Hypothesis: We hypothesized that higher PFAS exposures in the 1 st trimester would be associated with higher BP trajectory and faster BP velocity in later stages of pregnancy. Methods: We collected plasma from 1,308 individuals to measure six circulating PFAS in early pregnancy (median: 9.4 weeks gestation). Systolic BP (SBP) and diastolic BP (DBP) measurements, recorded from 12 weeks gestation until delivery, were abstracted from outpatient medical records. We estimated the mean BP trajectory via growth curve analysis, then employed BKMR to examine PFAS exposures with parameters of the trajectory – adjusting for age, race/ethnicity, pre-pregnancy BMI, income, parity, alcohol intake, and physical activity. We evaluated effect modification by age and BMI. Results: We collected a median of 13 BP measurements (IQR: 11 – 14) per participant. BKMR single PFAS analyses showed higher concentrations of PFOS were associated with higher SBP and DBP trajectory from 12 weeks gestation to delivery (Figure 1A) as well as faster SBP velocity. Stratified analyses showed evidence of effect modification. PFOS was associated with higher SBP trajectory in those with a BMI &lt; 25 kg/m 2 and higher DBP trajectory in those with a BMI ≥ 25 kg/m 2 (Figure 1B). In contrast, PFNA and PFHxS were associated with lower DBP trajectory for those with low BMI (Figure 1C). Lastly, exposure to lower quantiles of the PFAS mixture was associated with slower SBP velocity for those with low BMI. No associations were observed between PFAS and DBP velocity. Conclusions: Our findings suggest that select prenatal PFAS exposures may impact BP trajectories during pregnancy. Higher concentrations of PFOS are associated with higher BP trajectory and faster BP velocity. 1
Abstract P610: French Canadian Translation and Validation of the Eating in the Absence of Hunger Questionnaire for Children and Adolescents
Authors: Catherine Savard, Stéphanie Bégin, Julie Robitaille, Marie-France Hivert, Véronique Gingras
Journal: Circulation (2023)

Background: Eating in the absence of hunger (EAH), i.e. eating past the point of satiety, has been associated with the development of excess body weight during childhood, independently of other traditional risk factors. EAH is typically assessed with a laboratory-based standardized protocol which is time-consuming and requires important resources. A questionnaire has been developed to simplify the assessment of EAH among children and adolescents, but it has only been validated in English. Objective: Our aim was to validate a French translation of the EAH Questionnaire among children and adolescents in Montreal, Canada. Methods: Participants aged 7 to 15 years old completed the questionnaire upon recruitment (n=200) and ~4 weeks later (n=159 of 200, 80% of participants). Self-reported body weight and height data was also collected at inclusion and body mass index (BMI) z-scores were computed. The questionnaire includes 14 items divided into three subscales evaluating specific triggers of EAH (fatigue/boredom, negative affect and external cues). The global score for EAH ranges from 14 to 70 points, a higher score indicating a higher tendency to EAH. We assessed internal consistency for the full questionnaire and for each subscale using Cronbach alpha coefficients using data from the first completion of the questionnaire. Temporal stability was evaluated with Pearson correlations between the initial and second completions of the questionnaire, for each of the EAH subscales and for the total score. Association of EAH and BMI z-score was also assessed with Pearson correlation. Results: Participants (50% girls, 100 of 200; 71% white, 142 of 200) were 11.9 ± 2.3 years old, had a mean ±SD total score for EAH of 27.2 ± 9.1 points and a mean ±SD BMI z-score of 0.21 ± 1.05. The total EAH score and the negative affect subscale showed good internal consistency (Cronbach alpha = 0.88 and 0.86, respectively), while internal consistency for the fatigue/boredom and the external cues subscales was considered adequate (Cronbach alpha = 0.75 and 0.68, respectively). The total score and each subscale scores from the second completion of the questionnaire were significantly correlated with their respective scores from the first completion (r = 0.75; ρ &lt; 0.001 for the total score and r = 0.55 to 0.78; ρ &lt; 0.001 for the three subscales). Moreover, participants’ BMI z-score was positively correlated with EAH total score (r = 0.15; ρ = 0.03). Conclusion: A French translated version of the EAH questionnaire appears to represent an adequate and reliable tool to assess EAH among French-speaking Canadian children and adolescents.
Abstract P171: Associations Between Metals and Allostatic Load Among Non-Hispanic Asians and Non-Hispanic Whites From the National Health and Nutrition Examination Survey: 2015-2020
Authors: Austin Le, Rachel Morello-Frosch, Rosemarie de la Rosa
Journal: Circulation (2023)

Introduction: Environmental metal exposure has been linked with multi-system toxicity and elevated stress hormones, and high metal concentrations have been observed among Asian Americans. Metal exposure may also increase Allostatic Load (AL), or physiologic “wear-and-tear” on the body. Hypothesis: Metal biomarker concentration is associated with high AL among non-Hispanic Asian (NHA) and non-Hispanic White (NHW) adults. Methods: AL scores were calculated based on 9 biomarkers representing cardiovascular, metabolic, and immune system function using data from the National Health and Nutrition Examination Survey (2015-2020). High AL was defined as having ≥3 high-risk biomarkers based on empirically defined thresholds. Lead, cadmium, and mercury were quantified in blood while arsenic, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were measured in urine. Metal concentrations were categorized into empirically-defined sample tertiles. Survey-weighted logistic regression analyses controlled for demographic, socioeconomic, and health behavior variables. Analyses were also stratified by NHA and NHW. Results: The study sample consisted of 5,012 adults [mean age: 50.4, SE: 0.5] (21.6% foreign-born NHA, 2.7% US-born NHA, and 75.7% NHW). Prevalence of high AL was 38.2% among NHW, 32.4% among foreign-born NHA, and 19.3% among US-born NHA. Metal exposure demonstrated heterogenous relationships with AL ( Table ). Individuals in the highest tertile of cadmium exposure had 38% greater odds of having high AL than those in the lowest tertile, however this association was attenuated after controlling for socioeconomic status and health behaviors. Lead, mercury, arsenic, DMA, and MMA were associated with lower odds of high AL. Relationships were similar when stratified by NHW and NHA. Conclusion: The association between metals and AL differs by metal type in our study population. Future studies should explore the mechanistic pathways between high metal exposure and AL.